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Pain – Art and Science


Pain is an unpleasant  sensation originating from our physical and or emotional environments.


Faces of Pain


Extreme Physical Pain



Extreme Emotional Pain

Physical Pain

Pain is a symptom and as such reflects a derangement of either the external or internal environment.

All sensations start by stimulating a receptor of  a nerve that conducts the impulse to the spinal cord where low level control and discrimination occurs, and transfers  the stimulus to the brain, where higher centers process the stimulus and react to it.  The structures in the brain include the thalamus, somatosensory cortex, limbic system, and autonomic systems and they are involved in  perception, localization and integration.  They send out a stimulus with instructions of how to react which is executed by muscle contraction or tissue secretion.

Functionally, pain is protective. The physiology and pathophysiology relate to changing the mechanical stimulus into an electrical impulse, and then through a series of complex synapses the stimulus is transmitted with the intent of  protecting the person from further damage.

The causes of pain are innumerable and exist within the full spectrum of human diseases. Pain may result from pain receptors sensitive to pain, (pricking, cutting, tearing) extreme temperatures, pressure, or aberrant chemical environments. A myriad of processes then occur in response to tissue injury causing either irritation of a somatic nerve or distension and pressure on a visceral sensory nerve. Inflammation is one of the most common of these injurious processes that is classically and universally expressed with  pain – a concept first described by the second century philosopher Celsus.

The result of a pain impulse is usually withdrawal from the insulting stimulus, resting of the injured part, or seeking the help of a medical practitioner if the pain is unbearable and arises from an internal disorder.

Diagnosis of pain disorders should proceed with careful history taking and clinical examination, followed by appropriate laboratory tests, and imaging if necessary.

Pain is a very common symptom and most instances are treated with an analgesic or antiinflammatory agent.   For more serious pains, treatment is directed at the cause of the pain.



The table explores the variety of ways of classifying pain.  The left hand column reveals the classification based on functionality, origin, mode of stimulation, pathological causes and relationship of pain to chronicity.  As for functionality it may be adaptive or nonadaptive.  The pain may originate from somatic or visceral nociceptors, may originate from damaged nerves in which case it is called neuropathic, or it may be psychogenic.  The causes are usually via the inflammatory process but may result from any of the disease listed.

Structural Basis of Pain

A pain impulse is initiated by sensory receptors called nociceptors which are located in almost all the tissues. A noxious stimulus say from a hand touching a hot stove is then transmitted by sensory nerves to the spinal cord where a direct spinal reflex causes immediate withdrawal from the source. Additionally the stimulus is modified in the spinal cord by a variety of influences from other sources and is then transmitted via the midbrain and reticular activating system to the cortex. Finally, the stimulus reaches the brain’s somatosensory area where it is perceived and localized with additional extension to other areas of the cortex for the provision of a variety of protective reactions to the stimulus.

We will now expand the detail of the structural pathway described above.


Pain from the Joints


Pain from Sinuses 

The Sensory Pain Receptors – Nociceptors



A pain impulse is initiated by sensory receptors called nociceptors which are located in almost all the tissues. They are tree like branching structures.


Types of Receptors Subtending the A delta Fibers and C Fibers

The diagram shows sensory stimuli including sharp pressure, extreme heat and cold as well as chemical, stimulating the free nerve endings of the nociceptors  that are linked to the myelinated A delta fiber , and non myelinated C fiber.  The myelinated fiber will conduct the impulse between 3 and 15 times faster than the non myelinated fiber.

 These specialized receptors vary in structure and number throughout the tissue and viscera of the body. There are external nociceptors that are situated in the skin and cornea with higher concentrations in the coverings of the body including the skin, pleura, pericardium, peritoneum and periosteum. Internal nociceptors are found in muscles, joints, around blood vessels, and within the mucosa of some organs including the urinary bladder, genitourinary tract, and the gastrointestinal tract. There are nociceptors in varying concentrations in almost every organ in the body, but interestingly there are none in the brain substance itself .

First Order of Transmitting Sensory Fibers 

The first order of nerve fibers transport the stimulus from the nociceptor to the dorsal root ganglion


The sensory receptors of the nociceptors are found in the tissues peripherally and are connected  by a long fiber that transmits the impulse to the ganglion cell that lies in the dorsal ganglion in the neural canal alongside the spinal cord. This diagram shows the three types of receptors and fibers that transmit impulses related directly and indirectly to pain . The upper fiber is called the C fiber and it is non myelinated, consists of the receptors in the top left hand corner that when stimulated transmit the impulse via a long afferent neuron to the cell body lying alongside the spinal column. This fiber is relatively thin, measuring between .4 to 1.2 micrometers, and conducts the impulse at about 2m/s. The second neuron is the A delta fiber and it responds to the pricking or sharp sensation that is first felt and reacted to. It is weakly myelinated and is about 2-6 micro meters thick, and conducts the stimulus with a velocity of between 15-30 meters per second. The last fiber is the A beta fiber and it is responsible for the pressure component which indirectly affects response to pain by affecting the gate mechanism of pain. It is greater than 10 microns thick due to heavier myelination and conducts impulses at 30-100 meters per second

The Dorsal Root Ganglia


The Dorsal Root Ganglion of the Afferent Neurons

The dorsal root ganglion  is a focal accumulation of the first order nerve cells of the sensory component of the peripheral nerve. (orange)  It is situated  in the neural foramen of the vertebral body.  The central process emanates from the ganglion cell  and ends in the dorsal horn.

2nd  Order of Neurons

The second order sensory fibers are those fibers in the spinal cord.  They first cross to the contralateral side of the spinal cord and then connect to the thalamus via the spinothalamic tract. 


Second Order Neurons  – Cross Over in the Spinal Cord and 3rd order are Found in the  Spinothalamic Tract 

The spinothalamic tract is the major sensory ascending pathway of 2nd order neurons and serves as the major pathway for pain, temperature, itch and crude touch. Within its construct, the spinothalamic tract has three merging bands of specialized fibers that conduct pain impulses. The anterior spinothalamic tract carries pain signals initiated by touch while the lateral spinothalamic tract carries slow and fast fibers for pain and temperature sensations. The anterolateral spinothalamic pathway, located in the anterolateral white column pathway in the anterior half of the lateral funiculus conducts a variety of somatic pain signals.

3rd  Order of Neurons – Connect the Thalamus with the Sensory Cortex


The Three Orders of Neurons

Second Order Neurons From the Spinal Cord to the Brain and Perception of the Pain  The Three Orders of Neurons

 The stimulus is first converted into an electrical impulse which is taken by a first order sensory nerve (orange)  to the spinal cord (dorsal root ).  The second order neurons (blue) first transport the stimulus to the contralateral spinothalamic tract  which in turn transports the impulse  to the thalamus,.  The third order neurons (pink)  transport the impulse to the somatosensory cortex.

Role of the Thalamus


Thalamus – Relay Station to the Cortex in the Pain Pathway
The thalamus (T) is the gateway to the cerebral cortex. It is a paired organ and represents the main part of the diencephalon and subserves both motor and sensory function. It is structurally and functionally situated between the cortex and the midbrain. The thalamus has specific nuclei with diffuse projections to and from multiple regions of cerebral cortex.  The thalamus functions as a translator for the cerebral cortex. It processes sensory and motor information and mediates the autonomic nervous system regulating sleep and arousal. The thalamus also contains reciprocal connections to the cortex that are involved in consciousness. It may also play a role in vestibular function.  The thalamus translates pain signals of the 2nd order neurons and gives rise to the third order neurons that extend to the cortex. Awareness and localization of the pain is then achieved at the level of the cortex. The thalamus however is not merely a relay station for nociception but also plays a role in processing the stimulus.  Axons terminating in the lateral thalamus mediate discriminative aspects of pain (somatosensory cortex) including the originating body part. The fibers ending in the medial thalamus mediate the motivational and affective aspects relating for example to the emotional and memory of pain. These third order neurons travel to the prefrontal cortex, insular and cingulate gyrus which contribute to the emotion and memorization of pain experiences. 

The Homunculus Man and Localization of the Pain 


HOMUNCULUS MAN and Localization of Sensation in the Somatosensory Cortex of the Parietal Lobe

The homunculus man (literally the “little man”) is the distorted figure drawn to reflect the concept of size of organ paralleling the size of the sensory innervation. The diagram reflects the relative functional sensory space each body part occupies in the somatosensory cortex. Those structures with a high density of sensory receptors are represented by a larger size, while those with a lesser concentration of sensory apparatus are shown as being “smaller” in size. Hence the mouth lips, hands feet and genitalia have a relatively large representation. Nerve fibers from the spinothalamic tract in the spinal cord (blue line) are relayed to the thalamus (orange) which filters and then distributes the sensation to the somatosensory cortex.


The Somatosensory Cortex in the Parietal Lobe – Home of the Sensory Homunculus

The somatosensory cortex in the parietal lobe  is the location of the the main sensory receptive area for all the senses including pain. It receives the stimuli from the thalamus and then integrates the information with other parts of the brain  that will modify the perception of the sensation

The function of the somatosensory cortex is that of a higher processing center for touch, temperature, pain, and proprioception serving to amplify awareness of the sensations enabled by the thalamus. Sensation from the left side of the body are processed in the right somatosensory cortex and similarly those from the right side are processed on the left. The higher function of the somatosensory cortex allows us to localize the pain to a specific site, perceive the character and intensity of the stimulus, and sometimes helps identify the shape of the originating object.


The Higher Multicentric Levels of Pain Perception and Reaction

The somatosensory cortex relays impulses to other cerebral areas of perception that modulate the reaction to the pain  It forward the pain signals via the white matter to other centers in the cortex to enable integration with visual and auditory input, and with other higher cortical functions such as emotion and memory for example. The full experience is then “seen” by the brain enabling the consequent reaction to be as discriminating  and prudent relative to the nature and experience of the person. The difference between the reaction of an infant, child and an adult to the “shot at the doctors” speaks volumes about this latter function. 

Emotional Pain


Pain of Poverty

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Pain of Addiction


Pain of Loneliness

Pain .. Pain go away! – and please leave us alone!